Cancer Therapy by Silver Nanoparticles: Fiction or Reality?

As an emerging new class, metal nanoparticles and especially silver nanoparticles hold great potential in the field of cancer biology. Due to cancer-specific targeting, the consequently attenuated side-effects and the massive anti-cancer features render nanoparticle therapeutics desirable platforms for clinically relevant drug development. In this review, we highlight those characteristics of silver nanoparticle-based therapeutic concepts that are unique, exploitable, and achievable, as well as those that represent the critical hurdle in their advancement to clinical utilization. The collection of findings presented here will describe the features that distinguish silver nanoparticles from other anti-cancer agents and display the realistic opportunities and implications in oncotherapeutic innovations to find out whether cancer therapy by silver nanoparticles is fiction or reality.

Randomized trial of a portable HEPA air cleaner intervention to reduce asthma morbidity among Latino children in an agricultural community

Background Data on pediatric asthma morbidity and effective environmental interventions in U.S. agricultural settings are few. We evaluated the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children. Methods Seventy-five children with poorly controlled asthma and living in non-smoking homes were randomly assigned to asthma education alone or along with HEPA air cleaners placed in their sleeping area and home living room. The Asthma Control Test (ACT) score, asthma symptoms in prior 2 weeks, unplanned clinical utilization, creatinine-adjusted urinary leukotriene E4 (uLTE4 [ng/mg]), and additional secondary outcomes were evaluated at baseline, six, and 12 months. Group differences were assessed using multivariable-adjusted generalized estimating equations. Incident rate ratios of ever experiencing the metrics of poorer asthma health during follow-up (suboptimal asthma management) were estimated using Poisson regression models in secondary analysis. Results Mean child age was 9.2 and 8.6 years in intervention and control groups, respectively, and two-thirds of participants were male. Primary analysis of repeated measures of ACT score did not differ between groups (HEPA group mean change compared to controls 10% [95% CI: − 12-39%]). A suggestion of greater decrease in uLTE4 (ng/mg creatinine) was observed (− 10% [95% CI: − 20 -1%]). Secondary analysis showed children with HEPAs were less likely to have an ACT score meeting a clinically defined cutoff for poorly controlled asthma using repeated measures (IRR: 0.45 [95% CI: 0.21–0.97]). In Poisson models, intervention participants had reduced risk of ever meeting this cutoff (IRR: 0.43 [95% CI: 0.21–0.89]), ever having symptoms in the past 2 weeks (IRR: 0.71 [95% CI: 0.52–0.98]), and lower risk of any unplanned clinical utilization (IRR: 0.35 [95% CI: 0.13–0.94]) compared to control participants. Discussion The HAPI study showed generally improved outcomes among children in the HEPA air cleaner group. However, primary analyses did not meet statistical significance and many outcomes were subjective (self-report) in this unblinded study, so findings must be interpreted cautiously. HEPA air cleaners may provide additional benefit for child asthma health where traditional asthmagens (traffic, tobacco smoke) are not prominent factors, but larger studies with more statistical power and blinded designs are needed. Trial registration ClinicalTrials.gov Identifier: NCT04919915. Date of retrospective registration: May 19, 2021.

Prescription Patterns and Relationship to Pharmacogenomics Testing in the Military Health System

ABSTRACT Introduction Clinical utilization of pharmacogenomics (PGx) testing is highly institutionally dependent, and little information is known about provider practices of PGx testing in the Military Health System (MHS). In this study, we aimed to characterize Clinical Pharmacogenetics Implementation Consortium (CPIC) actionable prescription (Rx) patterns and their temporal relationship with PGx testing in the MHS. Methods Using data from the Military Health System Management Analysis and Reporting Tool (M2) database, this retrospective cohort study included all patients receiving at least one PGx test and at least one CPIC actionable Rx from January 2015 to August 2020 (845 patients, 1,471 PGx, 7,725 index CPIC actionable Rxs). Rx patterns and temporal relationships with PGx testing were characterized via descriptive statistics. Binomial regression was used to determine which patient and provider characteristics were associated with a patient receiving a PGx test within 30 days of an index Rx. Results Patients had a median of 9 index CPIC actionable Rx’s (range 1–26). Pain medications were most commonly prescribed (N = 794, 94% patients with at least 1 Rx). However, pain medication had the lowest Rx–PGx match rate (40%) compared to an average of 62% Rx–PGx match rate for all CPIC drugs. Antidepressants were also commonly prescribed (N = 668, 79.1% patients with at least 1 Rx), and antidepressants had the highest Rx–PGx match rate of 86.7%. A minority of providers (20%, N = 249) ordered the majority of PGx tests (86.1%, N = 1,266) and only 8.3% of PGx tests (N = 398) matched to a CPIC actionable drug within 30 days of the test (defined by Rxs ordered within 30 days before or after the PGx test). However, approximately 39.8% of patients (N = 317) had at least one drug match to a PGx test within 30 days. The largest predictor of whether a patient received a PGx test within 30 days of any index Rx was whether or not a specific psychiatry provider ordered the PGx test (odds ratio; OR 3.7, 95% CI 2.13–6.54, P < 0.001). Neither the CPIC level of evidence nor FDA PGx actionable or informative labels had a significant effect on PGx test timing. Conclusions PGx testing was generally limited to high Rx-drug users and was found to be an under-utilized resource. PGx testing did not typically follow CPIC guidelines. Implementing PGx testing protocols, simplifying PGx test-ordering by incorporating at minimum CYP2D6, CYP2C19, and CYP2C9 into PGx-testing panels, and unifying providers’ PGx knowledgebase in the MHS are feasible and would improve the clinical utilization of PGx tests in the MHS.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

A New Type of COP: The Role of Circulating Osteoprogenitor (COP) Cells in Health and Disease

Circulating osteogenic progenitor (COP) cells are a population of cells in the peripheral blood with the capacity for bone formation and broader differentiation into mesoderm-like cells in vitro. While some of their biological characteristics are documented in vitro, their role in the aging process and the pathogenesis of musculoskeletal diseases remains yet to be thoroughly evaluated. This translational session will go from bench to bedside, reviewing the current evidence on COP cells. In this session, we will provide an overview of the role of COP cells in the aging process and a number of physiological and pathological conditions and identify areas for future research. In addition, we will suggest possible areas for clinical utilization in the management of musculoskeletal diseases, which include novel diagnostic and therapeutic uses.

The Role and Challenges of Clinical Imaging During COVID-19 Outbreak

Objective: The Radiology department played a crucial role in detecting and following up with the COVID-19 disease during the pandemic. The purpose of this review was to highlight and discuss the role of each imaging modality, in the radiology department, that can help in the current pandemic and to determine the challenges faced by staff and how to overcome them. Materials and Methods: A literature search was performed using different databases, including PubMed, Google scholar, and the college electronic library to access 2020 published related articles. Results: A chest computed tomogram (CT) was found to be superior to a chest radiograph, with regards to the early detection of COVID-19. Utilizing lung point of care ultrasound (POCUS) with pediatric patients, demonstrated excellent sensitivity and specificity, compared to a chest radiography. In addition, lung ultrasound (LUS) showed a high correlation with the disease severity assessed with CT. However, magnetic resonance imaging (MRI) has some limiting factors with regard to its clinical utilization, due to signal loss. The reported challenges that the radiology department faced were mainly related to infection control, staff workload, and the training of students. Conclusion: The choice of an imaging modality to provide a COVID-19 diagnosis is debatable. It depends on several factors that should be carefully considered, such as disease stage, mobility of the patient, and ease of applying infection control procedures. The pros and cons of each imaging modality were highlighted, as part of this review. To control the spread of the infection, precautionary measures such as the use of portable radiographic equipment and the use of personal protective equipment (PPE) must be implemented.

Glycyrol Alone or in Combination with Gefitinib Is Effective against Gefitinib-Resistant HCC827GR Lung Cancer Cells

Gefitinib has been clinically demonstrated to be effective in the first-line setting for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired therapeutic resistance to gefitinib almost unavoidably develops, posing a major hurdle for its clinical utilization. Our previous study showed that glycyrol (GC), a representative of coumarin compounds isolated from the medicinal plant licorice, was effective against A549 lung cancer cells in both cell culture and a murine xenograft model. In this follow-up study, we evaluated the effect of glycyrol against gefitinib-resistant NSCLC and its ability to overcome the resistance using gefitinib-resistant HCC827GR cells. Results showed that glycyrol was effective against HCC827GR cells in both in vitro and in vivo. Moreover, glycyrol was able to significantly increase the sensitivity of HCC827GR cells to gefitinib, mechanistically associated with inactivating MET, which is a known important contributor to the resistance of HCC827GR cells to gefitinib. The findings of the present study suggest that glycyrol holds potential to be developed as a novel agent against gefitinib-resistant NSCLC.

Magnetic Resonance Texture Analysis in Myocardial Infarction

Texture analysis (TA) is a newly arisen field that can detect the invisible MRI signal changes among image pixels. Myocardial infarction (MI) is cardiomyocyte necrosis caused by myocardial ischemia and hypoxia, becoming the primary cause of death and disability worldwide. In recent years, various TA studies have been performed in patients with MI and show a good clinical application prospect. This review briefly presents the main pathogenesis and pathophysiology of MI, introduces the overview and workflow of TA, and summarizes multiple magnetic resonance TA (MRTA) clinical applications in MI. We also discuss the facing challenges currently for clinical utilization and propose the prospect.